- 期刊
- OpenAccess
Pharmacological Intervention by Exogenous Superoxide Dismutase Attenuates Diabetes-Induced Oxidative and Nitrosative Stress Mediated Renal Damage
聚乙二醇－超氧化抑制酶降低糖尿病引發氧化及硝化壓力導致的腎臟傷害
摘要
目標：本研究評估藥理上聚乙二醇－超氧化抑制酶(Superoxide dismutase, SOD-PEG)投予對糖尿病腎病變動物模型的治療效果。評估抗氧化劑介入對於oxidative stress、nitrosative stress、纖維化和細胞凋亡的影響。 方法：將Streptozotocin誘導的糖尿病老鼠隨機分配為SOD-PEG和賦形劑治療的兩組。分別去量測超氧化物(O2(上標 -)、一氧化氮(NO)、IL-1β和TGF-β1的生成。腎臟則以免疫組織化學和免疫染色加以分析。 結果：本研究證實了糖尿病顯著地增加了尿液中白蛋白的排出，同時也增加了糖尿病老鼠血中的超氧化物、IL-1β以及TGF-β1。有趣的是，外生性SOD-PEG的治療可以明顯地降低糖尿病的進展。在糖尿病的動物模型中，SOD的治療有效地降低了糖尿病老鼠腎臟的8-hydroxy-guandine表現，並且伴隨著TUNEL和PCNA染色的減低。進一步的研究顯示糖尿病腎臟的免疫染色有較高的peroxynitrite (OONO(上標 -))表現。外生性SOD的給予可以成功地減輕糖尿病腎臟傷害中peroxynitrite的過度表現。免疫組織化學分析顯示外生性SOD的治療可減輕TGF-β1和fibronectin的表現且降低糖尿病腎絲球中phospho-ERK和phospho-p38的表現。免疫染色則顯示可減緩nitrotyrosine、8-hydroxy-guandine、fibronectin和caspase-3蛋白在糖尿病老鼠腎臟中的表現。 結論：以外生性SOD去調節氧化還原反應或許是一個提供挽救因糖尿病誘發nitrosative和oxidative傷害所造成的腎臟細胞凋亡以及纖維化的方法。
並列摘要
Alias and hypothesis: This studs evaluated the rescue effect of pharmacological SOD administration on diabetic renal injury in an animal. The effect of antioxidant intervention by SOD-PEG on the indices of oxidative stress, nitrosative stress, fibrosis and apoptosis was assessed. Methods: The STZ-induced diabetic rats were randomly assigned to two groups: diabetes with SOD-PEG treatment and diabetes with vehicle treatment, Measurement of superoxide, NO, IL-1β and TGF-β1 production were carried out. Kidneys were harvested for immunohistochemical immunoblotting analysis. Results: This study demonstrated diabetes significantly increased urinary albumin excretion coinciding with increased systemic levels of superoxide IL-β and TGF-β1. Interestingly, exogenous SOD-PEG treatment significantly reduced the promotion effect of diabetes. In a diabetic animal model, SOD treatment effectively attenuated 8-hydroxy-guandine expression associated with reduced TUNEL and PCNA staining in the kidney of diabetic rats. Further studies showed higher ONOO(superscript -) expression in diabetic renal immunostaining. Exogenous SOD administration successfully lessened OONO(superscript -) over-expression in diabetic renal injury. Immunohistochemical observations showed exogenous SOD treatment attenuated TGF-β1, and fibronectin expression coincided with decreased phosphor-ERK and phosopho-p38 expression in diabetic renal glomeruli. Immunoblotting showed exogenous SOD alleviated nitrotyrosine, 8-hydroxy-guandine, fibronectin, and easpase-3 protein expression of kidney in diabetic rats. Conclusions: Ass alternative redox modulation strategy with exogenous SOD may provide a promising regimen for rescuing diabetes-promoted nitrosative and oxidative damages-related renal apoptosis and fibrosis.
延伸閱讀
- 吳珮羽（2019）。HN242藉由減少氧化壓力、抑制發炎反應和恢復心臟粒線體進而改善糖尿病心肌病〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU201901822
- Lee, P. H., Chang, H. H., Tung, C. W., Chang, H. Y., Hsu, Y. C., Lei, C. C., & Lin, C. L. (2010). N-乙醯基半胱氨酸(NAC)減緩糖尿病所引發氧化及硝化壓力所導致的腎臟傷害. Acta Nephrologica, 24(1), 13-23. https://www.airitilibrary.com/Article/Detail?DocID=10131671-201003-201011290090-201011290090-13-23
- Rinnno, H., Iijima, T., Takeda, Y., Shimizu, A., Kobata, M., Gohda, T., Saito, K., & Tomino, Y. (2002). 罹患高血壓的第二型糖尿病腎病受病人在使用血管張力素轉換酶抑制劑Temocapril之後血清Cystatin Chapi的變化. Acta Nephrologica, 16(2), 62-65. https://www.airitilibrary.com/Article/Detail?DocID=10131671-200204-16-2-62-65-a
- Shin, S. J., Hsieh, M. C., Wu, C. H., Chang, C. C., Chen, H. C., & Lai, Y. H. (2000). 高血糖能增加腎臟神經性一氧化氮合成脢mRNA表現而腎小管高葡萄糖不能. Acta Nephrologica, 14(4), 280-280. https://www.airitilibrary.com/Article/Detail?DocID=10131671-200010-14-4-280-280-o
- 李丹英、林亮羽（2020）。第二型鈉－葡萄糖轉運蛋白抑制劑：新一代糖尿病病患的腎臟救星。臨床醫學月刊，86(3)，559-569。https://doi.org/10.6666/ClinMed.202009_86(3).0102